Effects of the taxanes paclitaxel and docetaxel on edema formation and interstitial fluid pressure

Interstitial fluid pressure (P-if) is important for maintaining constant interstitial fluid volume. In several acute inflammatory reactions, a dramatic lowering of P-if has been observed, increasing transcapillary filtration pressure and favoring initial and rapid edema formation. This lowering of P-if seems to involve dynamic beta(1)-integrin-mediated interactions between connective tissue cells and extracellular matrix (ECM) fibers. beta(1)-Integrins are adhesion receptors responsible for the attachment of connective tissue cells to the ECM providing a force-transmitting physical link between the ECM and cytoskeleton. Disruption of actin filaments leads to lowering of P-if and edema formation, suggesting a role for actin filaments. The aim of this study was to further investigate the role of the cytoskeleton in the control of P-if by studying the effect of microtubuli fixation using paclitaxel and docetaxel. P-if was measured with the micropuncture technique. Albumin extravasation (E-alb) was measured using I-125-labeled albumin. Paclitaxel and docetaxel were tested locally on foot skin in female Wistar rats. Paclitaxel (6 mg/ml) reduced P-if from -1.5 +/- 1.0 mmHg in controls to -4.9 +/- 2.6 mmHg after 30 min (P < 0.05) in a dose-dependent manner (P < 0.05). Docetaxel caused a similar lowering of Pit. Both paclitaxel and docetaxel increased E-alb cornpared with Cremophor EL and saline control (P < 0.05). Pretreatment with phalloidin before paclitaxel, causing fixation of actin filaments. abolished the lowering of P-if caused by paclitaxel. This study confirms several previous studies demonstrating that connective tissue cells influence P-if and edema formation.